Asparagine Synthetase Deficiency

Alternative Names

  • ASNSD
  • ASNS Deficiency

Associated Genes

Asparagine Synthetase
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

615574

Mode of Inheritance

Autosomal recessive

Gene Map Locus

7q21.3

Description

ASNS deficiency is an autosomal recessive neurometabolic disorder of asparagine biosynthesis.  Affected patients display failure to thrive, microcephaly, delayed psychomotor development, progressive encephalopathy, and seizures.  Moreover, patients may experience an early death due to the disease severity.  The disorder may present in utero or at birth.  

The prevalence of the condition is less than 1 in 1,000,000 live births.  Diagnosis can be achieved through careful clinical examination, brain MRI, and biochemical analysis, which shows low level of asparagine, and molecular genetic testing.  Treatment is symptomatic.

Molecular Genetics

Mutations in the ASNS cause ASNSD.  The ASNS gene, located on the long arm of chromosome 7 codes for an asparagine synthetase enzyme which is involved in the synthesis of asparagine from glutamine and aspartate.  The absence of a functional enzyme results in a deficiency of asparagine, especially in the brain and CSF. 

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
615574.1United Arab EmiratesMaleNoYes Primary microcephaly ; Severe global dev... NM_133436.3:c.1193A>CHomozygousAutosomal, RecessiveBen-Salem et al. 2015
615574.2United Arab EmiratesMaleYesYes Global development delay; Seizure... NM_001673.4:c.146G>AHomozygousAutosomal, RecessiveSaleh et al. 2021 Affected cousin
615574.3United Arab EmiratesFemaleNoYes Global development delay; Microcephaly; ... NM_001673.4:c.146G>AHomozygousAutosomal, RecessiveSaleh et al. 2021

Other Reports

Saudi Arabia

Seidahmed et al., (2016) described two unrelated Saudi patients born to consanguineous parents with typical clinical and radiological presentations of ASNSD.  The first patient had microcephaly and facial dysmorphisms.  He developed abnormal movements after birth and died at the age of 1-month.  Brain MRI revealed cerebral atrophy.  Metabolic screening was negative.  He had a positive family history of four maternal aunts having died with similar presentations.  Whole exome sequencing identified a homozygous (Arg324*) mutation in the ASNS gene.  The second patient was a 4-year-old Saudi boy with microcephaly, dysmorphic features and abnormal movements.  He was found to have global developmental delay and spastic quadriplegia.  Whole exome sequencing revealed a novel mutation (p. Tyr315Cys) in the ASNS gene.  These two cases were found to expand the allelic heterogeneity of ASNSD.

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